Biomimetic nanoparticle synchronizing pyroptosis induction and mitophagy inhibition for anti-tumor therapy.
Biomaterials
; 301: 122293, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37639978
ABSTRACT
Inducing pyroptosis in cancer cells can result in a strong anti-tumor immune response. Our preliminary study indicates that pyroptosis can be temporarily strengthened by disrupting mitochondria, but ultimately diminished by defensive mitophagy. Here, this study reports a nano-system camouflaged with hybrid membranes consisting of homologous cell membrane and corresponding mitochondrial membrane, which is used to deliver a drug complex Ca@GOx consisting of calcium phosphate and glucose oxidase. By taking advantage of the homing effects of cell membrane and the orientated fusion mechanism of subcellular membrane, the nano-system is able to deliver Ca@GOx to mitochondria, induce mitochondrial Ca2+ overload and generate significant levels of ROS, thus leading to pyroptosis. However, it's found that this system exhibits limited anti-tumor effects in vivo due to the compensatory activation of mitophagy serving as negative feedback to pyroptosis. To address this issue, mitophagy-inhibiting chloroquine is loaded into nanoparticles to intensify pyroptosis. As a result, the combination significantly promotes tumor infiltration of CD8+T cells and improves anti-tumor effects. Together, this study establishes a rational combination of targeted mitochondria disruption and mitophagy blockage for effective pyroptosis-based therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomimética
/
Nanopartículas
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2023
Tipo de documento:
Article
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